Dental and endodontic filing materials and methods

ABSTRACT

Disclosed are endodontic filling materials and methods. A method for filling a dental root canal may include providing a hydrosetting filling material and inserting the hydrosetting filling material into the dental root canal, the material setting in the root canal to form a biocompatible filling. The hydrosetting filling material comprises a hydrogel former and a filler. The hydrogel former is at least one of a reactive organic hydrogel formers, an inorganic hydrogel formers, and a non-reactive organic hydrogel formers, and the filler is at least one of a self-hardening and a non-hardening filler. Plural filling material precursor compositions that collectively contain hydrogel formers and fillers may be provided.

CROSS REFERENCE TO RELATED APPLICATION

This application is a divisional of U.S. patent application Ser. No.14/805,137 entitled “Dental and Endodontic Filling Materials andMethods,” filed Jul. 21, 2015, which is a divisional of U.S. patentapplication Ser. No. 11/550,543, filed Oct. 18, 2006, and entitled“Dental and Endodontic Filling Materials,” now U.S. Pat. No. 9,101,436,which claims priority to U.S. provisional application Ser. No.60/728,838, filed Oct. 21, 2005, and entitled “Biocompatible EndodonticMaterials,”, the contents of which are incorporated by reference intheir entireties. Additionally, this application contains subject matterthat in some embodiments is related to some of the subject matterdescribed in U.S. provisional application Ser. No. 60/728,888, filedOct. 21, 2005, and entitled “Rapid Hardening Dual-Paste Premixed CalciumPhosphate Cements for Bone Defect Repair,”, and in U.S. patentapplication Ser. No. 11/550,586, filed Oct. 18, 2006, and entitled“Dual-Phase Cement Precursor Systems for Bone Repair,” now pending.These additional applications likewise are incorporated by reference intheir entireties.

STATEMENT OF FEDERALLY SPONSORED RESEARCH

The invention was made in the course of research supported at least inpart by Grant DE11789 from the National Institute of Dental andCraniofacial Research and carried out at the National Institute ofStandards and Technology. The U.S. government may have certain rights tothe invention.

TECHNICAL FIELD

This invention is in the field of dental and endodontic fillingmaterials and methods.

BACKGROUND OF THE INVENTION

The root canal is a channel in the tooth that runs from the crown to theroot in a normal tooth and that contains pulp, which is composed ofconnective tissue, nerves, and blood vessels. If the pulp is damaged bydisease, trauma, or invasion of decay, a root canal treatment isrecommended to avoid tooth loss. Treatment typically involves removal ofirritants, necrotic tissue, and infected material from the root canal,enlarging and sanitizing the canal, and finally the sealing the canal.The sealing generally is followed with a post canal treatment such as acrown.

In such endodontic treatment, sealers and filling materials aresometimes placed directly on or against vital tissues. Accordingly, itis highly desirable that a material that is used for such a filling orsealing purpose be highly biocompatible. Currently, zinc oxide-eugenol,glass ionomers, amalgams, composite resins, and mineral trioxideaggregates (MTA) are used for root-end and perforation repair. Of these,MTA is currently thought to be one of the more biocompatible materials;see Hauman C. H. J., Love R. M., Biocompatibility Of Dental MaterialsUsed In Contemporary Endodontic Therapy: A Review. Part 2 Root-CanalFilling Materials, Int. Endod. J. 36:147-160 (2003).

Apexification is an endodermic procedure that is related to the rootcanal procedure. In the apexification, a non-vital tooth with an openapex is filled with an interim filling material to control infection andto enable closure of the apex so that a definitive root canal treatmentcan be formed at a later time. Calcium hydroxide historically has beenused to establish apical closure and to avoid surgery in theapexification procedure; see Frank, A., Therapy For The DivergentPulpless Tooth By Continued Apical Formation, J. Am. Dent. Ass. 72:87-93(1966). Calcium hydroxide is effective, but requires high patientcompliance and multiple appointments extending over a long period oftime. Additionally, in connection with calcium hydroxide treatment,susceptibility to coronal leakage and fracture of the root has beenreported; see Weisenseel J. A. et al., Calcium Hydroxide As An ApicalBarrier, J. Endod. 13:1-5 (1987) and Schumacher J. W., Rutledge R. E.,An Alternative To Apexification, J. Endod. 19:529-531 (1993). A numberof studies demonstrate that MTA is effective in apexificationprocedures; see Kratchman, S., Perforation Repair And One-StepApexification Procedures, Dent. Clin. N. Am. 48 291-307 (2004); GiulianiV. et al.: The Use Of MTA In Teeth With Necrotic Pulps And Open Apices,Dent. Traumata. 18(4):217-21 (2002); Shabahang, S., Torabinejad, M.,Treatment Of Teeth With Open Apices Using Mineral Trioxide Aggregate,Pract. Periodont. Aesthe. Dent. 12(3):315-320 (2000). MTA, however, haspoor handling properties relative to calcium hydroxide, including longhardening times and a consistency that some deem too dry for delivery byinjection.

The invention seeks, in certain embodiments, to provide endodonticmaterials and methods useful for root canal and/or apexificationprocedures.

SUMMARY OF THE INVENTION

Generally, endodontic materials and methods are provided. The endodonticmaterials are single-paste hydrosetting filling materials orplural-paste filling material precursor compositions. When in the formof a single-paste material, the material comprises a hydrogel former anda filler, the hydrogel former in some embodiments being at least one ofa reactive organic hydrogel former, an inorganic hydrogel former, and anon-reactive hydrogel former, and the filler in some embodiments beingat least one of a self-hardening and a non-hardening filler. The fillingmaterial may be formed in situ in the root canal, or just prior toinsertion into the root canal, from plural precursor compositions. Inaccordance with these embodiments, at least first and second fillingmaterial precursors, upon blending and prior to setting, contain ahydrogel material and a filler. The hydrogel material is a hydrogelformer as described above, and optionally a stable hydrogel, andsimilarly, the filler is one or both of a self-hardening andnon-hardening filler as discussed hereinabove. Endodontic methods andkits likewise are contemplated in one or more of the various embodimentsof the invention.

BRIEF DESCRIPTION OF THE DRAWING

The FIGURE is a side elevational view of a mold in which the endodonticmaterials described in certain Examples were evaluated.

DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS

In some embodiments, the invention is directed towards an endodonticfilling material. It is contemplated that the filling material may beused in lieu of conventional filling materials, such as gutta percha,with a suitable separate sealer, such as any conventional sealer knownin the art. Alternatively, it is contemplated that the filling materialmay be used as a single endodontic filling material, without the needfor a separate sealer. Generally, it is contemplated that a superiortooth treatment, such as a post or crown, will be used to complete thetooth restorative efforts, although it is also contemplated that in someinstances no superior tooth treatment is employed. In many cases, it iscontemplated that the materials are of such consistency and viscositythat they can be delivered to the root canal by injection, possibly withthe assistance of a heating step.

A number of properties are desired for endodontic materials, and it iscontemplated in many embodiments that the materials used in conjunctionwith the claimed invention will satisfy most or all of these properties.Specifically, it is desired that the endodontic material be highlybiocompatible, by which is contemplated compatibility with both soft andhard tissues. Desirably, no chronic inflammatory tissue response isobserved using the materials. The materials should be resistant toleakage, and should provide a high level of sealing ability against thepenetration of bacteria and bacterial products. For similar reasons, thematerials themselves in many cases are highly alkaline, such that theyare able to neutralize the acid products of bacteria or of inflamedcells. Alkaline material may be incorporated as part of the filler inthe filling material; alternatively, in some embodiments, a separateantibacterial component may be employed. The filling materials should beinsoluble in normal physiological environments and under locally acidicconditions that may result upon exposure to bacteria or inflamed cells.The materials should be stable and resistant to washout in the rootcanal.

The endodontic materials generally are contemplated to set to form afilled hydrogel filling. Without intending to limit the invention to aparticular theory of operation, the hydrogel is believed to serve as acohesive and washout-resistant matrix for holding the filler particlesin place, thereby providing a stable mass for filling and sealing theroot canal. For certain reactive fillers, the hydrogel serves as anaqueous matrix to allow the fillers to take the form of a hardened mass.

Similarly, the hydrogel is believed to provide leakage resistance byfilling pores that ordinarily would otherwise be present in the fillingmaterial. Without intending to limit the invention to a particulartheory of operation, the fillers are believed to provide bulk andmechanical strength, thereby allowing the filling the material to besolid and stiff. Fillers provide leakage resistance and alkalinity, andcan provide radio opacity. For certain reactive hydrogels, the fillerprovides ionic calcium and/or alkalinity needed to react with polymers.Similarly, the filler is insoluble in the locally acidic environmentresulting from production of acid by bacteria or inflamed cells.

As heretofore stated, the filling materials may take the form ofsingle-paste filling materials or plural-paste filling materials. Theterm “paste” is not intended to be limiting or to necessarily connoteany adhesive properties other than those stated. When in the form of asingle paste filling material, the filling material should include ahydrogel former and a filler. Any suitable hydrogel former and fillermay be used in conjunction with the invention. In many embodiments, thehydrogel former includes a reactive organic hydrogel former, anon-reactive organic hydrogel former, or an inorganic hydrogel former.These embodiments are not mutually exclusive, and it is contemplated insome embodiments that plural types of hydrogel formers are included.

When an inorganic hydrogel former or a reactive organic hydrogel formeris employed, generally the filling material will be non-aqueous, bywhich is contemplated the complete or substantial absence of water tothe extent practicable, or the absence of water to the extent sufficientto provide a filling material that is stable prior to introduction intoa root canal. The inorganic or reactive organic hydrogel former may bedisposed in a non-aqueous liquid carrier. In such embodiments, after thematerial is placed into the root canal, water from surrounding tissuegradually replaced the non-aqueous liquid carrier, thereby allowing thereactive organic hydrogel former or the inorganic hydrogel former toform a hydrogel. In some cases, chemical reactions also occur betweenthe hydrogel former and the filler when the environment becomes aqueous,thus forming a hardened hydrogel.

Exemplary organic hydrogel formers include chitosans and biocompatiblederivatives thereof which are believed to form a hydrogel by settlingout of liquid phase due to an increase in pH produced by the dissolutionof fillers in an aqueous environment. Other hydrogel formers includealginates and pectinates, such as sodium alginate and sodium pectinate,which form a gel by cross-linking with calcium derived from thedissolution of soluble calcium-contained fillers in aqueous environment;and polyacrylic, poly-itaconic, or other poly-alkenoic acids orcopolymers thereof, the hardening of which generally requires a base andcalcium. The pectinates or alginates may be derived from pectinic andalginic acids. The liquid carrier may be any suitable non-aqueousmaterial such as ethanol, propanol, glycerol, certain polyethyleneglycols, and propylene glycol, these materials being liquid at 25° C.Exemplary inorganic hydrogel formers include tricalcium silicate,dicalcium silicate, and sodium silicate.

Alternatively, or in addition thereto, the filling material may includea non-reactive organic hydrogel former. Generally, such materialscomprise polymers that are blended in a non-aqueous liquid, such asthose hereinbefore described. After introduction into a root canal, thenon-aqueous liquid is gradually replaced by water that migrates fromsurrounding tissues. The polymer thus forms a hydrogel, but may notundergo a chemical reaction with the fillers. Exemplary non-reactiveorganic hydrogel formers include polyvinyl acetate, polyvinyl butyral,polyvinyl alcohols, hydroxymethyl cellulose, and konjac.

Mixtures of the foregoing types of hydrogel formers may be employed. Inother embodiments, the paste may include a formed hydrogel. In some suchembodiments, it may be desirable to heat the hydrogel to assist intransferring the filling material into a root canal, or to usemechanical assistance.

The filling material generally further includes a filler. Any suitablefiller may be used in conjunction with the invention. In manyembodiments, a self-hardening filler or non-hardening filler isemployed. These embodiments are not mutually exclusive, and it iscontemplated in some instances that both a self-hardening and anon-hardening filler may be employed.

Self-hardening fillers are those filling materials that do not harden ina non-aqueous environment, thereby allowing the filling material toremain soft and malleable in the provided package. These materials will,however, harden after being placed into a root canal, upon migration ofwater from surrounding tissues. Additionally, the self-hardening fillersmay further react with the hydrogels by providing ionic calcium, oralkalinity, or both. Exemplary self-hardening fillers are the variousself-setting calcium phosphate cements that have been reported in thescientific and patent literature, mineral trioxide aggregate (MTA),Portland cement, calcium silicates, and gypsum.

Non-hardening fillers are contemplated to include those fillers that, inthe absence of hydrogel former, do not harden readily upon exposure towater. Such fillers may react with a reactive hydrogel after thematerial is placed into the root canal by providing calcium oralkalinity as needed to cause the hydrogel former to form a hydrogel.Exemplary non-hardening fillers include hydroxyapatite, fluorapatite,tricalcium phosphate, calcium oxide, barium sulfate, bismuth sulfate,calcium hydroxide, calcium fluoride, calcium silicate, calciumgluconate, calcium glycerophosphate, tetracalcium phosphate, and calciumaluminate. For those hydrogel formers that form hydrogels with calcium,calcium fillers, such as the heretofore mentioned calcium compounds,calcium chloride, and calcium acetate, may be employed. Generally,whether a self-hardening or non-hardening filler is employed, the fillershould be selected to be consistent with the hydrogel former employed inthe filling material. For instance, when a chitosan hydrogel former isemployed, the filling material should include an alkaline species.Similarly, when a pectinate is employed, the filling material shouldinclude calcium. Those of skill in the art will recognize the variousworkable combinations of hydrogel formers and fillers that are suitablefor use and conjunction with the invention.

The filling material may include other suitable ingredients. Forinstance, one or more radio opaque fillers may be employed. The radioopaque filler may, for instance, be a suitable bismuth, barium, oriodide compound, such as barium sulfate or bismuth hydroxide.Additionally, other fillers in addition to those heretofore describedmay be employed. The filling material may include components that modifythe physical properties of the material, such as viscosity modifyingagents. In some embodiments, the filling material may includemedicaments or antibacterial agents, it being noted that some of thefillers are alkaline and possess antibacterial properties. Othersuitable antibacterial components include eugenol, iodide materials, andother biocompatible components with antibacterial properties. When acalcium silicate compound is employed, excess calcium silicate beyondthat needed for the hydrogel may function to an extent as a filler.

The filling material may be prepared from plural filling materialprecursor compositions, by which is contemplated that two or moreprecursor compositions, upon blending, form a filling material. Thevarious components may be present in any suitable amounts relative toone another. For instance, in some embodiments, the hydrogel former ispresent in an amount of 5-85% by weight, or in some cases 20-66%. Thefiller may, in some embodiments, be present in an amount of 15-95% byweight, and in some cases 34-80%.

When in the form of plural pastes, generally, the filling material isformed by blending the precursors in situ in the root canal orimmediately prior to application to the root canal. Each of the pastesmay be aqueous or at least substantially non-aqueous, as discussedhereinabove. In some embodiments, one of the pastes is aqueous and theother one of the pastes is non-aqueous. When aqueous, the aqueouscarrier may be water, saline, or, more generally, any suitable aqueouscarrier. In still further embodiments, more than two precursor pastesare employed, although more than two pastes may not be necessary in manyembodiments. The filling material precursor pastes form a fillingmaterial when mixed, the filling material containing a hydrogel formerand filler as discussed hereinabove. Generally, it is contemplated thatreactive organic hydrogel formers, non-reactive organic hydrogelformers, and inorganic hydrogel formers, and mixtures thereof, may beemployed in connection with the plural paste embodiments of theinvention. It is also contemplated that at least one of the pastes mayinclude a formed hydrogel. Similarly, it is contemplated thatself-hardening fillers and non-hardening fillers may be used inconjunction with these embodiments of the invention. The self-hardeningfiller may comprise plural components that harden upon introduction toone another; in these embodiments, one of the components may be presentin one of the precursor pastes and the other component may be present inanother precursor paste.

As with the single-paste filling materials, any one of the precursorpastes may contain additional components such as those describedhereinabove, including materials such as radio opaque fillers (bariumand bismuth sulfate being examples of such fillers), other fillers,antibacterial components, and components for modification of viscosityor other physical properties. Similarly, the amounts of hydrogel andfiller may be present in any suitable amounts in each paste relative toone another. Generally, if a non-aqueous paste is employed, the hydrogeland filler may in some embodiments be present in amounts similar tothose of the single-paste embodiments. For an aqueous paste, thehydrogel may be present in an amount of at least 5%, inclusive of water,and the filler may be present in any suitable amount, such as thebalance of weight of the paste.

In some embodiments, the filling material, whether provided in the formof a single-paste filling material or a multiple-paste filling materialprecursor system, may be provided in the form of a kit. When adual-paste system is employed, the kit may include the two pastes andseparate containers suitable to maintain the pastes separately. Ineither case, the kit may include a tool for introducing the fillingmaterial to a root canal. The tool may comprise, for instance, aconventional syringe. When multiple pastes are employed, amicrodispenser with a mixing tip, the mixing tip comprising anauger-like structure that allows the two pastes to be blended rapidlyand subsequently to be applied to the desired area, may be employed. Anexample of such a device is the Dual-Barrel 9 ml Micro Dispensing Systemby Tah Industries, Robbinsville, N.J. The invention contemplates the useof this device, or an analogous device that is specifically designed formedial usage. In some embodiments, the micro dispensers may include aregion that serves as the container for the pastes, by providingseparate holding chambers for the first and second pastes.

Each paste preferably is sufficiently stable to permit transport andreasonable storage prior to use. Stability may be measured by anytechnique or using any criteria deemed appropriate. In accordance withone such technique, a sample of the material or materials constitutingthe paste or pastes is heated to a temperature of 50° C., and held atthis temperature for seven days. The material then is used in theformation of a filling material, and the setting time of the material isevaluated as compared with the original setting time of a similarfilling material made without thermal treatment. If the setting time ofthe filling material made with the thermally treated phase isapproximately equal to the setting time of the similar filling material,the paste may be deemed suitably stable for use in conjunction with thepresent invention. The invention is not limited to pastes that meet thiscriterion; rather, the foregoing is provided to illustrate one of butmany possible methods for evaluating stability.

As heretofore described, in use, the filling materials may be employedin endodontic and specifically apexification procedures. The fillingmaterial may be placed into a root canal, and optionally sealed with asecondary sealer. When the filling material is formed from pluralprecursor pastes, the pastes may be injected or otherwise introducedsimultaneously into the root canal, or blended immediately prior toinsertion into the root canal. In various embodiments, the material isuseful generally as an endodontic material, as a filler or core, orsealer, as a material for retrofilling of root ends, for root canalperforation repairs, and in apexification procedures.

The following non-limiting Examples are provided to illustrate theinvention.

Examples 1-19 describe premixed hydrogel pastes.

Example 1

A hydrogel phase was prepared by blending 0.3 grams of chitosan malate(Vanson, Redmond, Wash., USA) with 1.2 grams of glycerol. The fillerphase was composed of 3 grams of Portland cement (the ingredient ofmineral trioxide aggregates, also known as MTA) and 0.3 grams of calciumoxide (CaO). The hydrogel and the fillers were then thoroughly mixed toform a filling material, and this filling material was stored in anairtight vial.

An aliquot of approximately 0.3 grams of the premixed filling materialwas placed into a cylindrical mold 1 (6 mm D×3 mm H). The top and bottomfaces of the mold were covered with fritted glass plates 2, as depictedin the FIGURE, and the assembly was placed in a 37° C. water bath toallow ingress of water into and egress of glycerol from the sample.Diffusion of water into the sample allowed Portland cement to dissolve,leading to an increase in the pH. The pH increase caused the chitosan tosettle out of the solution and to form a hard, rubber-like elastomericgel. The sample set within 20 minute and was demolded. The initialsetting of the sample was caused by the hardening of the chitosan. ThePortland cement in the filler phase hardened in about 1 to 2 hours. Thesample then was allowed to set fully by placing it into water at 37° C.for an additional 24 hours.

The fully set sample then was subjected to a dye penetration test. Thesample was placed in 5 mL of a 1% poly-R (Sigma Chemical, St Louis, Mo.)solution whose pH was adjusted to 7.4, and held at 37° C. for 3 days.Dye penetration into the sample, measured on fractured sample surfacesunder an optical microscope (25×), was 0.11 mm±0.11 mm (mean±s.d.; n=6).

The filling material of this Example may take the form of a prepackagedproduct that hardens rapidly after is placed in a root canal, where themoisture in the tissue will initiate the setting. This filling materialis significantly better than MTA-based filling materials currentlyavailable for endodontic treatments. It is highly cohesive and thereforecan be easily placed into the root canal, and it sets much faster thanconventional MTA-based filling materials.

Example 2

A hydrogel phase was prepared by blending 0.8 grams of chitosan malate(Vanson, Redmond, Wash., USA) with 1.2 grams of glycerol. The fillerphase was composed of 1.5 grams of fluorapatite and 1.5 grams of CaO.The hydrogel and the fillers were then thoroughly mixed and stored in anairtight vial. An aliquot of approximately 0.3 grams of the premixedmaterial was placed in a cylindrical mold and into a water bath asdescribed in Example 1. Diffusion of water into the sample allowed CaOto dissolve, leading to an increase in the pH. The increased pH causedthe chitosan to settle out of the solution, forming a hard gel. Thesample set within 15 minute and was demolded. The sample was allowed tofully set by placing it into water at 37° C. for an additional 24 hours,and was then subjected to a dye penetration test as described above. Dyepenetration into the sample was 0.38 mm±0.17 mm (mean±s.d.; n=6).

Although the fillers did not harden, the material had a hard,rubber-like consistency, and was chemically and dimensionally stable.The cement of this Example can be used as a prepackaged product thathardens rapidly after it is placed in a root canal, where the moisturein the tissue will initiate setting. This material is significantlybetter than many currently available endodontic materials treatmentsbecause it is highly biocompatible, it is cohesive, and it sets rapidly.

Example 3

The hydrogel phase was prepared by blending 0.2 grams of konjacGlucomannan powder (Konjac Foods, Sunnyvale, Calif.) with 0.8 grams ofglycerol. The filler phase was composed of 2 grams of a self-hardeningcalcium phosphate cement (CPC) powder that included 72.6% tetracalciumphosphate and 27.4% dicalcium phosphate anhydrous. The hydrogel and thefillers were then thoroughly mixed and stored in an airtight vial. Analiquot of approximately 0.3 grams of the premixed material was placedin a cylindrical mold and the assembly placed in a water bath as inExample 1. The sample set within 2 hours and was demolded. The samplewas allowed to fully set by placing it into water at 37° C. for anadditional 24 hours and was then subjected to a dye penetration test asdescribed above. Dye penetration into the sample was 0.38 mm±0.17 mm(mean±s.d.; n=6). This material also is an excellent endodontic fillingmaterial.

Example 4

A non-reactive hydrogel was prepared by blending 0.1 grams ofpolyvinylbutyral powder (mw=88,000, Scientific Polymer Products, Inc.,Ontario, N.J.) with 0.4 grams of n-propyl alcohol (Mallinckrodt). Thefiller phase contained 1 gram of a self-hardening calcium phosphatecement (CPC) powder that was composed of 72.6% tetracalcium phosphateand 27.4% dicalcium phosphate anhydrous, 0.25 grams of groundtetracalcium phosphate, and 0.25 grams of Ca₃SiO₅. The hydrogel and thefillers were thoroughly mixed and stored in an airtight vial. A mold wasprepared and subjected to a dye penetration test as described above. Dyepenetration into the sample was 0.04 mm±0.03 mm (mean±s.d.; n=5). Inthis example, Ca₃SiO₅ primarily plays the role of a filler that providesalkalinity.

Examples 5-7

A non-reactive hydrogel containing 0.5 grams of polyvinylbutyral powder(mw=88,000, Scientific Polymer Products, Inc., Ontario, N.J.) dissolvedin 1.5 grams of absolute ethanol was provided. A premixed paste wasprepared by mixing the hydrogel and a Portland cement powdered fillerthoroughly at a ratio (g/g) (P/L) of 3. A mold was prepared and bathedas described above. The sample was demolded after 4 hours and was placedinto water at 37° C. for an additional 20 h, and subsequently subjectedto a dye penetration test as described above. Seven-day dye penetrationinto the sample was 0.05 mm (n=5).

Samples were also prepared using P/L=2 (Example 6) and 1 (Example 7). Inthese cases, the dye penetration were 0.08 mm and 0.63 mm (n=5),respectively.

Examples 8-10

A non-reactive hydrogel was prepared by dissolving 0.2 grams ofpolyvinylbutyral powder (mw=88,000, Scientific Polymer Products, Inc.,Ontario, N.J.) in 1.8 grams of absolute ethanol. A premixed paste wasprepared by mixing the hydrogel and a Portland cement powdered fillerthoroughly at a ratio (g/g) (P/L) of 3. The paste was molded and bathedas described above. The sample was demolded after 4 hours and placedinto water at 37° C. for an additional 20 h It was subjected to a dyepenetration test as described above. Seven-day dye penetration into thesample was 0.03 mm (n=5). The test was repeated, except that the sampleswere held for 37° C. for one week. No significant difference in testresults was observed.

Samples were also prepared using P/L=2 (Example 9) and 1 (Example 10).In these cases, the dye penetration were 0.09 mm and 0.44 mm (n=5),respectively.

Example 11

A non-reactive hydrogel was prepared by blending 2.5 grams of polyvinylacetate powder (PVAc) (mw=45,000, Polysciences, Inc., Warrington, Pa.)with 7.5 mL of absolute ethanol. A non-hardening filler phase that wascomposed of 2 grams of fluorapatite (FA) (General Electric Company,Cleveland, Ohio) and 1 grams of CaO (Fisher Scientific, Fair Lawn, N.J.)was prepared. The hydrogel and the fillers were thoroughly mixed andstored in an airtight vial. The material was molded and bathed asdescribed above, then demolded after 18 hours and placed into water at37° C. for an additional 48 hours. The molded filler material wasobserved to be slightly swelled. Dye penetration into the sample was0.18 mm±0.09 mm (mean±s.d.; n=6). For this and the following Examples,the samples were in the dye solution for at least three days, sometimesthree to five days.

Example 12-19

The following Examples were performed, and dye penetration results wereobserved. The hydrogels in these Examples were prepared as describedabove.

Dye Hydrogel Control— Fillers Penetration¹ 1 g glycerol 2.2 gCa₄(PO₄)₂O + >1.5 (without polymer) 0.8 g CaHPO₄ 12 1.6 g chitosanmalate + 1.5 g CPC² + 1.5 g CaO 0.38 ± 0.24 2.4 g glycerol 13 0.1 g Naalginate + 3.2 g CPC + Ig CaO 0.10 ± 0.08 0.9 g glycerol 14 PVAc³ +ethanol⁴ 3 g CPC 0.07 ± 0.01 15 0.375 g PVB⁵ + 3 g Portland cement 0.02± 0.03 1.125 g ethanol 16 0.25 PVB + 2 g CPC + 1 g CaO 0.35 ± 0.20 0.75g ethanol 17 0.385 g PAAc⁶ + 3 g CPC 0.16 ± 0.08 1.155 g water 18 0.1 gPVB⁵ + 1.5 g CPC + 0.1 g 0.26 ± 0.08 0.4 g ethanol Na₃PO₄•12H₂O 19 0.1 gPVB⁵ + 1 g CPC + 0.5 g TTCP + 0.13 ± 0.05 0.4 g ethanol 0.15 gNa₃PO₄•12H₂O ¹values are in mm (mean ± s.d.; n = 6) ²CPC was composed of72.6% tetracalcium phosphate and 27.4% dicalcium phosphate anhydrous³polyvinyl acetate (mw = 45,000, Polysciences Inc., Warrington, PA)⁴water free ethanol (200 proof) ⁵polyvynylbutyral (mw = 88,000,Scientific Polymer Products, Inc., Ontario, NJ) ⁶polyacrylic acid (mw =240,000) came with liquid (25%) (Aldrich Chemical Company, Inc.,Milwaukee, WI).

Examples 20-33 describe two-paste systems.

Example 20

A non-aqueous paste that contained 0.6 grams of chitosan malate in 0.9grams of glycerol as a reactive hydrogel precursor and 3 grams ofPortland cement as a self-hardening filler system was provided. Alsoprovided was an aqueous paste that contained 0.05 grams of poly vinylalcohol (PVA) dissolved in 0.45 grams of water as a non-reactivehydrogel and 2 grams of fluorapatite (FA) as a non-hardening filler.Upon combination of the two pastes, chitosan malate dissolved in thewater and formed a hardened gel within 7 min with the aid of basederived from Portland cement. Additionally, the water from the aqueousphased allowed Portland cement to harden. Because water was provided byone of the pastes, the mold described above was not used. For settingtime measurement in this and the following two-paste examples, the mixedpaste was placed into a stainless steel mold (6 mm d×3 mm high) that wascovered with two regular glass plates and left in 100% humidity air at37° C. The sample was allowed to fully set by placing it into water at37° C. for an additional 24 hours and was then subjected to a dyepenetration test as described above. Dye penetration into the sample was0.31 mm±0.09 mm (mean±s.d.; n=6).

Example 21

A non-aqueous paste that contained 0.6 grams of chitosan malate in 0.9grams of glycerol as a reactive hydrogel precursor and 2 grams oftetracalcium phosphate (TTCP) as an incomplete portion of aself-hardening (TTCP+DCPA) calcium phosphate cement filler system wasprovided. Also provided was an aqueous paste that contained 0.056 gramsof PVA dissolved in 0.5 grams of water as a non-reactive hydrogel and 1gram of dicalcium phosphate anhydrous (DCPA) as the other portion of thecalcium phosphate cement filler system. Once the two pastes werecombined, chitosan lactate dissolved in the water and formed a hardenedgel within 15 min with the aid of base derived from TTCP. Additionally,the TTCP and DCPA react to form hardened cement with hydroxyapatite asthe product. The sample was molded as described above, and was allowedto fully set by placing it into water at 37° C. for an additional 24hours and was then subjected to a dye penetration test as describedabove. Dye penetration into the sample was 0.17 mm±0.10 mm (mean±s.d.;n=6).

Example 22

In this Example, the non-aqueous paste contained 0.6 grams of chitosanmalate in 0.9 grams of glycerol as a reactive hydrogel precursor and 2grams of FA as a non-hardening filler. The aqueous paste contained 0.1grams of PVA dissolved in 0.9 grams of water as a non-reactive hydrogeland 2 grams of TTCP as a non-reactive filler. The two pastes werecombined and allowed to set, then allowed to fully set by placing itinto water at 37° C. for an additional 24 hours. Dye penetration intothe sample was 0.35 mm±0.08 mm (mean±s.d.; n=6).

Example 23

In this Example, the non-aqueous paste contained 0.6 grams of chitosanmalate in 0.9 grams of glycerol as a reactive hydrogel precursor, 2.5grams of Portland cement as a self-hardening filler system, and 0.5grams of calcium chloride as a soluble calcium source. The aqueous pastecontained 0.2 grams of sodium alginate in 0.8 grams of water as areactive hydrogel and 1 gram of FA as a non-hardening filler. Once thetwo pastes were combined, the paste hardened within 10 minutes. Thehardening mechanisms included (1) chitosan malate dissolved in the waterand formed a hardened gel with the aid of base derived from Portlandcement, (2) the alginate gel hardened by cross linking with the calciumfrom the calcium chloride originally present in the non-aqueous paste,and (3) the water from the aqueous allowed Portland cement to harden.The sample was allowed to fully set by placing it into water at 37° C.for an additional 24 hours and was then subjected to a dye penetrationtest as described above. Dye penetration into the sample was 0.35mm±0.07 mm (mean±s.d.; n=6).

Example 24

In this Example, the non-aqueous pastes contained 0.1 grams of sodiumalginate in 0.9 grams of glycerol as a reactive hydrogel precursor, 2grams of tetracalcium phosphate (TTCP) as an incomplete portion of aself-hardening (TTCP+DCPA) calcium phosphate cement filler system, and0.5 grams calcium chloride to cause alginate hardening. The aqueouspaste contained 0.5 grams of polyacrylic acid (PAAc) (Aldrich ChemicalCompany, Inc., Milwaukee, Wis.) dissolved in 0.5 grams of water as areactive hydrogel and 1 gram DCPA as the other portion of the calciumphosphate cement filler system. The two pastes were combined, whereuponthe PAAc gel hardened due to the alkalinity of TTCP and the calcium fromboth TTCP and DCPA. Additionally, sodium alginate dissolved in water andformed a hardened gel by cross linking with the calcium from the calciumchloride. The material set after about 15 minutes. The sample wasallowed to fully set by placing it into water at 37° C. for anadditional 24 hours and was then subjected to a dye penetration test asdescribed above. Although dye appeared to have completely penetratedinto the sample, the intensity of the dye was extremely low.

Example 25

In this Example, the non-aqueous paste contained 0.25 grams of polyvinylbutyral (PVB) in 0.75 grams of ethanol as a non-reactive hydrogelprecursor and 3 grams of Portland cement as a self-hardening fillersystem. The aqueous paste contained 0.05 grams of sodium polyvinylalcohol (PVA) in 0.45 grams of water as a non-reactive hydrogel and 1.5grams of FA as a non-hardening filler. Once the two pastes werecombined, the water allowed the Portland cement to harden in 10 min. Thesample was allowed to fully set by placing it in water at 37° C. for anadditional 24 hours and was then subjected to a dye penetration test asdescribed above. Dye penetration into the sample was 0.38 mm±0.17 mm(mean±s.d.; n=6).

Example 26

In this Example, the non-aqueous pastes contained 0.25 grams of PVB in0.75 grams of absolute ethanol as a non-reactive hydrogel precursor andtetracalcium phosphate (TTCP) as an incomplete portion of aself-hardening (TTCP+DCPA) calcium phosphate cement filler system. Theaqueous paste contained 0.05 grams of PVA dissolved in 0.45 grams ofwater as a non-reactive hydrogel and 1 gram of dicalcium phosphateanhydrous (DCPA) as the other portion of the calcium phosphate cementfiller system. Once the two pastes were combined, the paste hardened inabout 5 min. TTCP and DCPA reacted to form hardened cement withhydroxyapatite as the product. The sample was allowed to fully set byplacing it into water at 37° C. for an additional 24 hours and was thensubjected to a dye penetration test as described above. Dye penetrationinto the sample was 0.27 mm±0.18 mm (mean±s.d.; n=6).

Example 27

In this Example, the non-aqueous paste contained 0.25 grams of PVB in0.75 grams of absolute ethanol as a non-reactive hydrogel precursor and2 grams of Portland cement as a self-hardening filler system. Theaqueous paste contained 0.15 grams of chitosan malate in 0.85 grams ofwater as a reactive hydrogel and 1.5 grams of FA as a non-hardeningfiller. Once the two pastes were combined, chitosan malate hardened dueto the base from the Portland cement, and the water allowed Portlandcement to harden. After 5 min, it was placed into water. The sample wasallowed to fully set by placing it into water at 37° C. for anadditional 24 hours and was then subjected to a dye penetration test asdescribed above. Dye penetration into the sample was 0.46 mm±0.26 mm(mean±s.d.; n=6).

Example 28

In this Example, the non-aqueous paste contained 0.3 grams of Ca₃SiO₅ in0.2 grams of glycerol. The aqueous paste contained 1 gram of DCPA in 0.5grams of 0.5 M Na₂HPO₄ solution. Once the two pastes are combined, thephosphate solution allowed Ca₃SiO₅ and DCPA to react and harden. After40 min, the hardened filler material was placed into water at 37° C. Thesample was allowed to fully set by placing it into water at 37° C. foran additional 24 hours and was then subjected to a dye penetration testas described above. Dye penetration into the sample was 0.02 mm±0.02 mm(mean±s.d.; n=5).

Example 29

The non-aqueous paste of this Example contained 0.6 grams of Ca₃SiO₅ in0.4 grams of glycerol. The aqueous paste contained 1.79 grams of DCPA in0.93 grams of 1.5 M NaH₂PO₄ solution. Once the two pastes were combined,the phosphate solution allowed Ca₃SiO₅ and DCPA to react and harden.After 15 min, the hardened filler material was placed into water at 37°C. The sample was allowed to fully set by placing it into water at 37°C. for an additional 24 hours and was then subjected to a dyepenetration test as described above. Dye penetration into the sample was0.001 mm±0.001 mm (mean±s.d.; n=5).

Example 30

The non-aqueous paste of this Example contained 1.4 grams oftetracalcium phosphate (TTCP) as an incomplete portion of aself-hardening (TTCP+DCPA) calcium phosphate cement filler system, 0.6grams of Ca₃SiO₅, and 0.2 grams of Na₂HPO₄, in 1.17 grams of glycerol.The aqueous paste contained 1 gram of dicalcium phosphate anhydrous(DCPA) as the other portion of the calcium phosphate cement fillersystem, 1.2 grams of BaSO₄, and 0.165 grams of chitosan lactate in 0.935grams of water. Once the two pastes were combined, chitosan lactateformed a hardened gel within 60 min with the aid of base derived fromTTCP. Additionally, the TTCP and DCPA reacted to form a hardened cementwith hydroxyapatite as the product. Na₂HPO₄ crystals promoted thesetting reaction. The filler material sample was allowed to fully set byplacing it into water at 37° C. for an additional 24 hours and was thensubjected to a dye penetration test as described above. Dye penetrationinto the sample was 0.05 mm±0.02 mm (mean±s.d.; n=5).

Example 31

In this Example, the non-aqueous paste contained 1.5 grams of aself-hardening calcium phosphate cement filler system and 0.5 grams ofCa₃SiO₅ in 1.2 grams of glycerol. The aqueous paste contained 0.75 gramsof monocalcium phosphate monohydrate (MCPM), 0.75 grams BaSO₄, 0.1 gramsof chitosan lactate, and 0.11 grams of glycerol in 0.9 grams of water.Once the two pastes were combined, chitosan lactate formed a hardenedgel within 10 min with the aid of base derived from Ca₃SiO₅.Additionally, the TTCP and DCPA reacted to form hardened cement withhydroxyapatite as the product. The filler material sample was allowed tofully set by placing it into water at 37° C. for an additional 24 hoursand was then subjected to a dye penetration test as described above. Dyepenetration into the sample was 0.04 mm±0.03 mm (mean±s.d.; n=5).

Example 32

In this Example, the non-aqueous paste contained 3 grams of Portlandcement in 1.2 grams of glycerol. The aqueous paste contained 2 grams ofMCPM and 0.1 grams of glycerol in 1 gram of 8.5 M glycolic acidsolution. Once the two pastes were combined, the water allowed thePortland cement to harden. The filler material hardened at 9.3 min±0.6min (mean±s.d.; n=3). The sample was allowed to fully set by placing itinto water at 37° C. for an additional 24 hours and was then subjectedto a dye penetration test as described above. Dye penetration into thesample was 0.001 mm±0.001 mm (mean±s.d.; n=5).

Example 33

The non-aqueous paste of this Example contained 0.6 grams of Ca₃SiO₅ in0.4 grams of glycerol. The aqueous paste contained 1.2 grams of MCPM in0.5 grams of 8.5 M glycolic acid solution. Once the two pastes werecombined, MCPM reacted with Ca₃SiO₅, and also glycolic acid formed acalcium salt, which hardened. After 10 min, the hardened filler materialwas placed into water at 37° C. The sample was allowed to fully set byplacing it into water at 37° C. for an additional 24 hours and was thensubjected to a dye penetration test as described above. Dye penetrationinto the sample was 0.02 mm±0.02 mm (mean±s.d.; n=5).

Compositions similar to the compositions given in the followingadditional examples are described in copending application Ser. No.11/550,586, filed Oct. 18, 2006, entitled “DUAL-PHASE CEMENT PRECURSORSYSTEMS FOR BONE REPAIR”.

Example 34

The non-aqueous paste contains 3 grams of Portland cement as aself-hardening filler in 1.22 grams of glycerol. The aqueous pastecontains 1.508 grams of MCPM and 0.23 grams of chitosan lactate in 1.31grams of water. Once the two pastes are combined, chitosan lactatehardens due to the base from Portland cement and the water allowsPortland cement to harden. After 5 min, it was placed into water. Thesample was allowed to fully set by placing it into water at 37° C. foran additional 24 hours and was then subjected to a dye penetration testas described above. Dye penetration into the sample was 0.006 mm±0.007mm (mean±s.d.; n=5).

Example 35

Paste 1 was prepared by blending 3 g of MCPM into 1.35 g of an aqueoussolution containing 0.15 g of chitosan lactate. Paste 2 was composed of3 g of a calcium phosphate cement (CPC) mixture (containing 73 wt % TTCPand 27 wt % DCPA) and 1.2 g of glycerin. The combined pastes hardened in5.7 min±1.2 min (mean±s.d.; n=3), and was placed in water at 37° C. Thesample was allowed to fully set by placing it into water at 37° C. foran additional 24 hours and was then subjected to a dye penetration testas described above. Dye penetration into the sample was 0.03 mm±0.03 mm(mean±s.d.; n=5).

Example 36

Paste 1 was prepared by blending 3 g of MCPM into two liquids, the firstliquid being 4.8 g of an aqueous solution containing 8.5M glycolic acidand 10 wt % chitosan lactate, and the second liquid being 2 g ofglycerin. Paste 2 was composed of 3 g of a calcium phosphate cement(CPC) mixture (containing 73 wt % TTCP and 27 wt % DCPA) and 1.2 g ofglycerin. Once the two pastes were combined, chitosan lactate hardeneddue to the base from the CPC, and the water allowed CPC to harden. Also,glycolic acid reacted with calcium from CPC to form a calcium salt.After 10 min, the sample was placed into water at 37° C. The sample wasallowed to fully set by placing it into water at 37° C. for anadditional 24 hours and was then subjected to a dye penetration test asdescribed above. Dye penetration into the sample was 0.02 mm±0.02 mm(mean±s.d.; n=5).

Example 37

The non-aqueous paste contains 3 grams of Portland cement in 1.2 gramsof glycerol. The aqueous paste contains 3 grams of MCPM and 0.4 grams ofchitosan lactate in 3.6 grams of 8.5 M glycolic acid. Once the twopastes are combined, chitosan lactate hardens due to the base fromPortland cement and the water allows Portland cement to harden. Alsoglycolic acid reacts with Ca from CPC to form Ca-salt. After 5 min, itwas placed into water at 37° C. The sample was allowed to fully set byplacing it into water at 37° C. for an additional 24 hours and was thensubjected to a dye penetration test as described above. Dye penetrationinto the sample was 0.05 mm±0.04 mm (mean±s.d.; n=5).

Example 38

The non-aqueous paste contains 3.01 grams of Portland cement in 1.22grams of glycerol. The aqueous paste contains 3 grams of MCPM, 0.017grams of HPMC, and 0.5 grams of glycerol in 1.5 grams MCPM-DCPDsaturated solution. Once the two pastes are combined, the water allowsPortland cement to harden. Also MCPM reacts with Portland cement to formhydroxyapatite. After 5 min, it was placed into water at 37° C. Thesample was allowed to fully set by placing it into water at 37° C. foran additional 24 hours and was then subjected to a dye penetration testas described above. Dye penetration into the sample was 0.04 mm±0.05 mm(mean±s.d.; n=5).

It is thus seen that, in certain embodiments, the invention provides aroot canal filling material. In other embodiments, endodontic methodsare provided.

All references, including publications, patent applications, andpatents, cited herein are hereby incorporated by reference. In anylisting of possible ingredients or components, mixtures of the possibleingredients or components are contemplated unless expressly indicatedotherwise. The description of certain embodiments as “preferred”embodiments, and other recitation of embodiments, features, or ranges asbeing preferred, is not deemed to be limiting, and the invention isdeemed to encompass embodiments that are presently deemed to be lesspreferred. All methods described herein can be performed in any suitableorder unless otherwise indicated herein or otherwise clearlycontradicted by context. The use of any and all examples, or exemplarylanguage (e.g., “such as”) provided herein, is intended to illuminatethe invention and does not pose a limitation on the scope of theinvention unless otherwise claimed. Any statement herein as to thenature or benefits of the invention or of the preferred embodiments isnot intended to be limiting, and the appended claims should not bedeemed to be limited by such statements. More generally, no language inthe specification should be construed as indicating any non-claimedelement as being essential to the practice of the invention. Thisinvention includes all modifications and equivalents of the subjectmatter recited in the claims appended hereto as permitted by applicablelaw. Moreover, any combination of the above-described elements in allpossible variations thereof is encompassed by the invention unlessotherwise indicated herein or otherwise clearly contradicted by context.The description herein of any reference or patent is not intended toconstitute a concession that such reference is available as prior artagainst the present invention.

We claim:
 1. A two-paste phase composition for filling a dental rootcanal, comprising: a non-aqueous paste phase, comprising: a reactivehydrogel precursor chosen from a group consisting of chitosan malate andsodium alginate, and a self-hardening filler system chosen from a groupconsisting of Portland cement, tetracalcium phosphate and calciumphosphate mixture, calcium chloride, and mixtures thereof; and anaqueous paste phase comprising; a non-reactive hydrogel chosen from agroup consisting of polyvinyl alcohol, sodium alginate, polyacrylicacid, and sodium polyvinyl alcohol, and a non-reactive, non-hardeningfiller chosen from a group consisting of fluorapatite, dicalciumphosphate anhydrous, and tetracalcium phosphate.